This program project focuses research clinicians and basic neurobiology investigators on the analysis and modeling of human epileptogenic tissue. The surgically resected tissue will come from two well-defined human seizure disorders, temporal lobe epilepsy associated with medial temporal sclerosis (medial temporal lobe epilepsy (MTLE), and epilepsy associated with chronic tumors (tumor associated epilepsy (TAE). Experimental neurobiological techniques will be used to address specific hypotheses relating to the electrophysiology, anatomy, and biochemistry of the hippocampus and parahippocampus in MTLE and of the tumor with surrounding cortex in TAE. The program is divided into three major sections. The first defines the tissues' electrophysiological characteristics using depth electrodes and intraoperative recording and stimulating techniques (Project 1, S. Spencer). This same tissue is then studied in slice preparations asking similar questions at an intracellular and network level (Project 2, A. Williamson). The second section uses immunohistochemical, autoradiographical, and molecular techniques to characterize structure (Project 3, N. de Lanerolle). Data from all three projects is correlated and compared with a heat-kindled rat model (Project 3, N. de Lanerolle). The third section studies the neurobiology of ion-regulating proteins in the tissue of these two human focal epileptic conditions attempting to understand what cellular (particularly glial) events predispose to neuronal death and resultant excitability and more specifically, Dr. A. Cornell-Bell (Project 5) will characterize glial Ca++ physiology and glutamate pharmacology in human and animal tissue using optical imaging techniques.